Chirality change after constraint geometry minimization using MMFF #5292

petrucci86 · 2022-05-15T18:39:56Z

petrucci86
May 15, 2022

It was found that the the chirality of the molecule changes after running geometry minimization (MMFF) with constraint geometry. Is there any way to force the molecule stays in the same chirality during the minimization? Any thoughts? Thanks

ptosco · 2022-05-15T20:15:26Z

ptosco
May 15, 2022
Collaborator

@petrucci86 This should not happen, unless the starting conformation is highly strained in its original stereochemical configuration.
Would you be able to share the 3D coordinates of your molecule (as SDF or MOL file) ahead of the minimisation? Thanks.

1 reply

petrucci86 May 15, 2022
Author

Thanks for the reply. Please find the mol file below (before and after minimization):

Before minimization:

CREYON CCC TRIMER
     RDKit          3D

106111  0  0  0  0  0  0  0  0999 V2000
    5.6659    4.7730    0.7721 P   0  0  0  0  0  5  0  0  0  0  0  0
    4.9288    6.0326    0.8088 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.8241    4.6642    1.9536 O   0  0  0  0  0  1  0  0  0  0  0  0
    4.6453    3.4096    0.7551 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.0287    2.5001    1.7765 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.2205    1.2733    0.8543 C   0  0  1  0  0  0  0  0  0  0  0  0
    6.4084    1.6759    0.1057 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.9500    0.5876   -0.4413 C   0  0  2  0  0  0  0  0  0  0  0  0
    6.3457   -0.6372    0.3119 C   0  0  1  0  0  0  0  0  0  0  0  0
    5.6674    0.0461    1.4655 C   0  0  2  0  0  0  0  0  0  0  0  0
    4.6077   -0.6334    2.0564 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.5279   -1.3415    1.1736 P   0  0  0  0  0  5  0  0  0  0  0  0
    2.2429   -1.4973    2.0756 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.8850   -3.0680    0.9555 O   0  0  0  0  0  1  0  0  0  0  0  0
    2.9151   -0.8461   -0.2759 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.6455   -0.2177   -0.0934 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7978   -1.0600   -1.1097 C   0  0  1  0  0  0  0  0  0  0  0  0
    1.0623   -2.3761   -0.5541 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0569   -3.0883   -0.8115 C   0  0  2  0  0  0  0  0  0  0  0  0
   -1.1498   -2.1516   -0.2985 C   0  0  1  0  0  0  0  0  0  0  0  0
   -0.6118   -0.8348   -0.8728 C   0  0  2  0  0  0  0  0  0  0  0  0
   -1.2970   -0.7328   -2.1024 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.4272    0.4215   -2.0948 P   0  0  0  0  0  5  0  0  0  0  0  0
   -1.8732    1.8203   -1.6826 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8687    0.7201   -3.7722 O   0  0  0  0  0  1  0  0  0  0  0  0
   -3.8793    0.2290   -1.3653 O   0  0  0  0  0  0  0  0  0  0  0  0
   -3.9266    0.7877   -0.0570 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.1678    1.7293   -0.2908 C   0  0  1  0  0  0  0  0  0  0  0  0
   -6.0114    0.9290   -1.0053 O   0  0  0  0  0  0  0  0  0  0  0  0
   -7.1390    0.7884   -0.2957 C   0  0  2  0  0  0  0  0  0  0  0  0
   -6.7182    0.7814    1.1598 C   0  0  1  0  0  0  0  0  0  0  0  0
   -5.7642    1.9599    1.1026 C   0  0  2  0  0  0  0  0  0  0  0  0
   -6.5962    3.1049    0.9819 O   0  0  0  0  0  0  0  0  0  0  0  0
   -5.9609    4.3434    0.0874 P   0  0  0  0  0  5  0  0  0  0  0  0
   -6.2740    4.1167   -1.4264 O   0  0  0  0  0  0  0  0  0  0  0  0
   -4.3462    4.6662    0.2998 O   0  0  0  0  0  1  0  0  0  0  0  0
   -6.8442    5.7621    0.4327 O   0  0  0  0  0  0  0  0  0  0  0  0
   -8.1612    5.3990    0.6410 C   0  0  0  0  0  0  0  0  0  0  0  0
   -7.7851    1.1169    1.9968 O   0  0  0  0  0  0  0  0  0  0  0  0
   -8.1941   -0.0063   -0.7344 N   0  0  0  0  0  0  0  0  0  0  0  0
   -8.9709   -0.6163    0.1938 C   0  0  0  0  0  0  0  0  0  0  0  0
  -10.2420   -1.0409   -0.1735 C   0  0  0  0  0  0  0  0  0  0  0  0
  -10.6421   -0.8461   -1.4558 C   0  0  0  0  0  0  0  0  0  0  0  0
   -9.8494   -0.2824   -2.3726 N   0  0  0  0  0  0  0  0  0  0  0  0
   -8.6078    0.1473   -1.9854 C   0  0  0  0  0  0  0  0  0  0  0  0
   -7.9156    0.6668   -2.8886 O   0  0  0  0  0  0  0  0  0  0  0  0
  -12.0595   -1.0416   -1.7728 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3658   -2.5100   -0.9112 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1868   -4.3388   -0.1653 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.3577   -4.6301    1.0701 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.1837   -5.8725    1.6230 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.5279   -6.8459    0.9694 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0699   -6.5478   -0.2603 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8692   -5.3045   -0.7653 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4073   -5.1193   -1.8981 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7599   -8.1408    1.5024 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.4920   -1.2663   -0.5537 O   0  0  0  0  0  0  0  0  0  0  0  0
    8.3789    0.3918   -0.4780 N   0  0  0  0  0  0  0  0  0  0  0  0
    8.9378   -0.0590   -1.6573 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.2439   -0.4680   -1.6734 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.0000   -0.4392   -0.5599 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.4547    0.0186    0.5974 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.1301    0.4349    0.6281 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.6731    0.8361    1.7090 O   0  0  0  0  0  0  0  0  0  0  0  0
   12.3300   -1.0170   -0.5302 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.3928    4.6824   -0.8172 O   0  0  0  0  0  0  0  0  0  0  0  0
    7.7398    4.7499   -0.7951 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.1790    2.2746    2.4454 H   0  0  0  0  0  0  0  0  0  0  0  0
    5.9414    2.7338    2.2559 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.4746    1.2256    0.0722 H   0  0  0  0  0  0  0  0  0  0  0  0
    6.5767    0.5432   -1.5099 H   0  0  0  0  0  0  0  0  0  0  0  0
    7.1719   -1.2752    0.6264 H   0  0  0  0  0  0  0  0  0  0  0  0
    6.3784    0.1869    2.2796 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.2906   -0.3346    0.8744 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.6470    0.8295   -0.4652 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.1975   -0.9266   -2.0854 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2317   -3.2330   -1.8945 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2205   -2.1835    0.7771 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9100   -0.0149   -0.1884 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.2049    0.0580    0.7069 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0627    1.3414    0.1750 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.7282    2.5930   -0.7393 H   0  0  0  0  0  0  0  0  0  0  0  0
   -7.6287    1.9098   -0.3211 H   0  0  0  0  0  0  0  0  0  0  0  0
   -6.2316   -0.1563    1.4159 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.9850    2.0602    1.8253 H   0  0  0  0  0  0  0  0  0  0  0  0
   -8.1978    4.3338    0.9704 H   0  0  0  0  0  0  0  0  0  0  0  0
   -8.5914    6.0038    1.4782 H   0  0  0  0  0  0  0  0  0  0  0  0
   -8.8002    5.4607   -0.2697 H   0  0  0  0  0  0  0  0  0  0  0  0
   -7.5038    0.7485    2.8961 H   0  0  0  0  0  0  0  0  0  0  0  0
   -8.5798   -0.7555    1.1787 H   0  0  0  0  0  0  0  0  0  0  0  0
  -10.8521   -1.5298    0.5642 H   0  0  0  0  0  0  0  0  0  0  0  0
  -12.4326   -1.6425   -2.4652 H   0  0  0  0  0  0  0  0  0  0  0  0
  -12.7127   -0.4140   -1.1860 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.2554   -2.5080   -1.8881 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.9141   -3.8896    1.6079 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.5883   -6.0801    2.5922 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0503   -8.8840    1.2227 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5154   -8.4067    2.1059 H   0  0  0  0  0  0  0  0  0  0  0  0
    6.0085   -1.5997   -1.3218 H   0  0  0  0  0  0  0  0  0  0  0  0
    8.3689   -0.1065   -2.5651 H   0  0  0  0  0  0  0  0  0  0  0  0
   10.7568   -0.8185   -2.5790 H   0  0  0  0  0  0  0  0  0  0  0  0
   13.1956   -0.5892   -0.8125 H   0  0  0  0  0  0  0  0  0  0  0  0
   12.3860   -2.0450   -0.1676 H   0  0  0  0  0  0  0  0  0  0  0  0
    8.2947    3.9031   -0.3751 H   0  0  0  0  0  0  0  0  0  0  0  0
    8.0930    5.6917   -0.2850 H   0  0  0  0  0  0  0  0  0  0  0  0
    8.0754    4.8072   -1.8767 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  1  3  1  0
  1  4  1  0
  4  5  1  0
  5  6  1  0
  6  7  1  0
  7  8  1  0
  8  9  1  0
  9 10  1  0
 10 11  1  0
 11 12  1  0
 12 13  2  0
 12 14  1  0
 12 15  1  0
 15 16  1  0
 16 17  1  0
 17 18  1  0
 18 19  1  0
 19 20  1  0
 20 21  1  0
 21 22  1  0
 22 23  1  0
 23 24  2  0
 23 25  1  0
 23 26  1  0
 26 27  1  0
 27 28  1  0
 28 29  1  0
 29 30  1  0
 30 31  1  0
 31 32  1  0
 32 33  1  0
 33 34  1  0
 34 35  2  0
 34 36  1  0
 34 37  1  0
 37 38  1  0
 31 39  1  0
 30 40  1  0
 40 41  1  0
 41 42  2  0
 42 43  1  0
 43 44  2  0
 44 45  1  0
 45 46  2  0
 43 47  1  0
 20 48  1  0
 19 49  1  0
 49 50  1  0
 50 51  2  0
 51 52  1  0
 52 53  2  0
 53 54  1  0
 54 55  2  0
 52 56  1  0
  9 57  1  0
  8 58  1  0
 58 59  1  0
 59 60  2  0
 60 61  1  0
 61 62  2  0
 62 63  1  0
 63 64  2  0
 61 65  1  0
  1 66  1  0
 66 67  1  0
 10  6  1  0
 21 17  1  0
 32 28  1  0
 45 40  1  0
 54 49  1  0
 63 58  1  0
  5 68  1  0
  5 69  1  0
  6 70  1  6
  8 71  1  6
  9 72  1  1
 10 73  1  1
 16 74  1  0
 16 75  1  0
 17 76  1  6
 19 77  1  6
 20 78  1  1
 21 79  1  1
 27 80  1  0
 27 81  1  0
 28 82  1  6
 30 83  1  1
 31 84  1  1
 32 85  1  1
 38 86  1  0
 38 87  1  0
 38 88  1  0
 39 89  1  0
 41 90  1  0
 42 91  1  0
 47 92  1  0
 47 93  1  0
 48 94  1  0
 50 95  1  0
 51 96  1  0
 56 97  1  0
 56 98  1  0
 57 99  1  0
 59100  1  0
 60101  1  0
 65102  1  0
 65103  1  0
 67104  1  0
 67105  1  0
 67106  1  0
M  CHG  4   3  -1  14  -1  25  -1  36  -1
M  END

After minimization:


CREYON CCC TRIMER
     RDKit          3D

106111  0  0  0  0  0  0  0  0999 V2000
   -7.5564   -0.8074   -3.3736 P   0  0  2  0  0  5  0  0  0  0  0  0
   -7.5341   -2.1498   -4.0730 O   0  0  0  0  0  0  0  0  0  0  0  0
   -7.0147    0.4252   -4.0661 O   0  0  0  0  0  1  0  0  0  0  0  0
   -6.8160   -0.9450   -1.9225 O   0  0  0  0  0  0  0  0  0  0  0  0
   -7.0842   -2.0745   -1.1012 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.4042   -1.9189    0.2560 C   0  0  2  0  0  0  0  0  0  0  0  0
   -6.8679   -0.6970    0.8712 O   0  0  0  0  0  0  0  0  0  0  0  0
   -5.7883   -0.2005    1.7083 C   0  0  1  0  0  0  0  0  0  0  0  0
   -4.6083   -1.1671    1.5307 C   0  0  2  0  0  0  0  0  0  0  0  0
   -4.8821   -1.7858    0.1716 C   0  0  1  0  0  0  0  0  0  0  0  0
   -4.2646   -3.0512    0.0037 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8494   -3.1957   -0.8104 P   0  0  1  0  0  5  0  0  0  0  0  0
   -2.5459   -4.6774   -0.9151 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.9418   -2.3705   -2.0785 O   0  0  0  0  0  1  0  0  0  0  0  0
   -1.7020   -2.5094    0.1360 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2965   -3.1324    1.3513 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3235   -2.2611    2.1591 C   0  0  2  0  0  0  0  0  0  0  0  0
   -0.9029   -0.9942    2.4879 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.1530   -0.0044    2.5078 C   0  0  1  0  0  0  0  0  0  0  0  0
    1.4506   -0.7389    2.1548 C   0  0  2  0  0  0  0  0  0  0  0  0
    0.9602   -1.9503    1.3789 C   0  0  1  0  0  0  0  0  0  0  0  0
    1.8727   -3.0356    1.4215 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.9091   -3.3082    0.1802 P   0  0  2  0  0  5  0  0  0  0  0  0
    2.1398   -3.1848   -1.1201 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.6375   -4.6023    0.4859 O   0  0  0  0  0  1  0  0  0  0  0  0
    4.0036   -2.0912    0.2175 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.9674   -2.0084    1.2622 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.7936   -0.7189    1.1848 C   0  0  2  0  0  0  0  0  0  0  0  0
    4.9879    0.4574    1.2727 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.5732    1.5002    0.4685 C   0  0  1  0  0  0  0  0  0  0  0  0
    6.8453    0.9100   -0.1394 C   0  0  2  0  0  0  0  0  0  0  0  0
    6.5689   -0.5858   -0.1221 C   0  0  1  0  0  0  0  0  0  0  0  0
    7.7586   -1.3547   -0.1050 O   0  0  0  0  0  0  0  0  0  0  0  0
    8.3566   -1.9744   -1.4990 P   0  0  1  0  0  5  0  0  0  0  0  0
    9.5634   -2.8226   -1.1549 O   0  0  0  0  0  0  0  0  0  0  0  0
    7.2230   -2.5674   -2.3089 O   0  0  0  0  0  1  0  0  0  0  0  0
    8.8655   -0.6144   -2.2493 O   0  0  0  0  0  0  0  0  0  0  0  0
    9.9910    0.0905   -1.7535 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.9186    1.2356    0.7457 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.6357    2.0240   -0.5402 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.5344    1.2978   -0.9369 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.6554    1.7648   -1.8214 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.9201    3.1189   -2.3665 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.9697    3.8079   -2.0061 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.8760    3.3026   -1.0907 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.8648    3.9646   -0.7679 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.0269    3.6412   -3.2725 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.0355   -1.1418    3.3960 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1116    1.1226    1.5937 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0064    1.0043    0.5533 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2499    2.0042   -0.2916 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.5030    3.2649   -0.0598 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.3532    3.3823    0.9195 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.5975    2.3300    1.7839 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.4196    2.4547    2.6943 O   0  0  0  0  0  0  0  0  0  0  0  0
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   -4.7176   -2.1463    2.5661 O   0  0  0  0  0  0  0  0  0  0  0  0
   -5.3959    1.1837    1.3832 N   0  0  0  0  0  0  0  0  0  0  0  0
   -5.7030    1.7476    0.1654 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.3131    2.9773   -0.1656 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.5225    3.7190    0.8478 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.2302    3.1918    2.0064 N   0  0  0  0  0  0  0  0  0  0  0  0
   -4.6418    1.9120    2.3319 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.3449    1.4259    3.4254 O   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0964    4.9896    0.5394 N   0  0  0  0  0  0  0  0  0  0  0  0
   -9.0879   -0.5140   -2.8761 O   0  0  0  0  0  0  0  0  0  0  0  0
   -9.3898    0.7294   -2.2652 C   0  0  0  0  0  0  0  0  0  0  0  0
   -8.1678   -2.1459   -0.9618 H   0  0  0  0  0  0  0  0  0  0  0  0
   -6.7302   -2.9788   -1.6058 H   0  0  0  0  0  0  0  0  0  0  0  0
   -6.6967   -2.7634    0.8930 H   0  0  0  0  0  0  0  0  0  0  0  0
   -6.1562   -0.2085    2.7415 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.6176   -0.7133    1.6066 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.5871   -1.0893   -0.6207 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8253   -4.0911    1.1110 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1871   -3.3291    1.9501 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0924   -2.7867    3.0946 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.1913    0.4006    3.5265 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.1916   -0.1476    1.6131 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.7332   -1.6592    0.3474 H   0  0  0  0  0  0  0  0  0  0  0  0
    5.6288   -2.8784    1.1947 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.4460   -2.0486    2.2189 H   0  0  0  0  0  0  0  0  0  0  0  0
    6.4839   -0.7159    2.0386 H   0  0  0  0  0  0  0  0  0  0  0  0
    5.8125    2.3267    1.1490 H   0  0  0  0  0  0  0  0  0  0  0  0
    7.0993    1.2955   -1.1304 H   0  0  0  0  0  0  0  0  0  0  0  0
    5.9360   -0.8485   -0.9769 H   0  0  0  0  0  0  0  0  0  0  0  0
   10.2402   -0.2145   -0.7341 H   0  0  0  0  0  0  0  0  0  0  0  0
    9.7725    1.1608   -1.7683 H   0  0  0  0  0  0  0  0  0  0  0  0
   10.8457   -0.1083   -2.4049 H   0  0  0  0  0  0  0  0  0  0  0  0
    8.6809    0.6893    0.4956 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.3919    0.3169   -0.5065 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.7855    1.2054   -2.1388 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.1690    4.5632   -3.6705 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.2015    3.1311   -3.5691 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.7240   -1.7961    3.1993 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5193    0.0610    0.4300 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9505    1.9243   -1.1121 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2400    5.2011   -0.7888 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3904    4.2615   -1.6781 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.1291   -2.8831    2.3375 H   0  0  0  0  0  0  0  0  0  0  0  0
   -6.2742    1.1571   -0.5366 H   0  0  0  0  0  0  0  0  0  0  0  0
   -5.5438    3.4310   -1.1203 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5498    5.5295    1.2017 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.3043    5.4251   -0.3530 H   0  0  0  0  0  0  0  0  0  0  0  0
   -8.7362    0.8980   -1.4060 H   0  0  0  0  0  0  0  0  0  0  0  0
   -9.2712    1.5387   -2.9899 H   0  0  0  0  0  0  0  0  0  0  0  0
  -10.4274    0.7077   -1.9232 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  1  3  1  1
  1  4  1  0
  4  5  1  0
  5  6  1  0
  6  7  1  0
  7  8  1  0
  8  9  1  0
  9 10  1  0
 10 11  1  0
 11 12  1  0
 12 13  2  0
 12 14  1  1
 12 15  1  0
 15 16  1  0
 16 17  1  0
 17 18  1  0
 18 19  1  0
 19 20  1  0
 20 21  1  0
 21 22  1  0
 22 23  1  0
 23 24  2  0
 23 25  1  6
 23 26  1  0
 26 27  1  0
 27 28  1  0
 28 29  1  0
 29 30  1  0
 30 31  1  0
 31 32  1  0
 32 33  1  0
 33 34  1  0
 34 35  2  0
 34 36  1  1
 34 37  1  0
 37 38  1  0
 31 39  1  0
 30 40  1  0
 40 41  1  0
 41 42  2  0
 42 43  1  0
 43 44  2  0
 44 45  1  0
 45 46  2  0
 43 47  1  0
 20 48  1  0
 19 49  1  0
 49 50  1  0
 50 51  2  0
 51 52  1  0
 52 53  2  0
 53 54  1  0
 54 55  2  0
 52 56  1  0
  9 57  1  0
  8 58  1  0
 58 59  1  0
 59 60  2  0
 60 61  1  0
 61 62  2  0
 62 63  1  0
 63 64  2  0
 61 65  1  0
  1 66  1  0
 66 67  1  0
 10  6  1  0
 21 17  1  0
 32 28  1  0
 45 40  1  0
 54 49  1  0
 63 58  1  0
  5 68  1  0
  5 69  1  0
  6 70  1  6
  8 71  1  6
  9 72  1  1
 10 73  1  1
 16 74  1  0
 16 75  1  0
 17 76  1  6
 19 77  1  6
 20 78  1  1
 21 79  1  1
 27 80  1  0
 27 81  1  0
 28 82  1  6
 30 83  1  6
 31 84  1  1
 32 85  1  1
 38 86  1  0
 38 87  1  0
 38 88  1  0
 39 89  1  0
 41 90  1  0
 42 91  1  0
 47 92  1  0
 47 93  1  0
 48 94  1  0
 50 95  1  0
 51 96  1  0
 56 97  1  0
 56 98  1  0
 57 99  1  0
 59100  1  0
 60101  1  0
 65102  1  0
 65103  1  0
 67104  1  0
 67105  1  0
 67106  1  0
M  CHG  4   3  -1  14  -1  25  -1  36  -1
M  END

ptosco · 2022-05-16T06:07:55Z

ptosco
May 16, 2022
Collaborator

@petrucci86 Would you mind editing your comment above and pasting again the two MOL blocks, this time inserting the two blocks between triple back quotes as below:

MOL block between triple back quotes

Doing so will avoid that the formatting is stripped and save me reformatting work.
Thanks!

1 reply

petrucci86 May 16, 2022
Author

Thanks. I did. Please let me know if I still missed something.

ptosco · 2022-05-16T19:59:57Z

ptosco
May 16, 2022
Collaborator

@petrucci86 Thank you.
I have just minimized the structure, and chirality is retained. I suspect that you might not have perceived stereochemistry from 3D coordinates ahead of running the minimization. In that case, the chiral centers would be treated as being unconstrained and hence allowed to invert. See below what I did:

from rdkit import Chem
from rdkit.Chem import AllChem

before_min = Chem.MolFromMolBlock("""CREYON CCC TRIMER
     RDKit          3D

106111  0  0  0  0  0  0  0  0999 V2000
    5.6659    4.7730    0.7721 P   0  0  0  0  0  5  0  0  0  0  0  0
    4.9288    6.0326    0.8088 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.8241    4.6642    1.9536 O   0  0  0  0  0  1  0  0  0  0  0  0
    4.6453    3.4096    0.7551 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.0287    2.5001    1.7765 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.2205    1.2733    0.8543 C   0  0  1  0  0  0  0  0  0  0  0  0
    6.4084    1.6759    0.1057 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.9500    0.5876   -0.4413 C   0  0  2  0  0  0  0  0  0  0  0  0
    6.3457   -0.6372    0.3119 C   0  0  1  0  0  0  0  0  0  0  0  0
    5.6674    0.0461    1.4655 C   0  0  2  0  0  0  0  0  0  0  0  0
    4.6077   -0.6334    2.0564 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.5279   -1.3415    1.1736 P   0  0  0  0  0  5  0  0  0  0  0  0
    2.2429   -1.4973    2.0756 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.8850   -3.0680    0.9555 O   0  0  0  0  0  1  0  0  0  0  0  0
    2.9151   -0.8461   -0.2759 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.6455   -0.2177   -0.0934 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7978   -1.0600   -1.1097 C   0  0  1  0  0  0  0  0  0  0  0  0
    1.0623   -2.3761   -0.5541 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0569   -3.0883   -0.8115 C   0  0  2  0  0  0  0  0  0  0  0  0
   -1.1498   -2.1516   -0.2985 C   0  0  1  0  0  0  0  0  0  0  0  0
   -0.6118   -0.8348   -0.8728 C   0  0  2  0  0  0  0  0  0  0  0  0
   -1.2970   -0.7328   -2.1024 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.4272    0.4215   -2.0948 P   0  0  0  0  0  5  0  0  0  0  0  0
   -1.8732    1.8203   -1.6826 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8687    0.7201   -3.7722 O   0  0  0  0  0  1  0  0  0  0  0  0
   -3.8793    0.2290   -1.3653 O   0  0  0  0  0  0  0  0  0  0  0  0
   -3.9266    0.7877   -0.0570 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.1678    1.7293   -0.2908 C   0  0  1  0  0  0  0  0  0  0  0  0
   -6.0114    0.9290   -1.0053 O   0  0  0  0  0  0  0  0  0  0  0  0
   -7.1390    0.7884   -0.2957 C   0  0  2  0  0  0  0  0  0  0  0  0
   -6.7182    0.7814    1.1598 C   0  0  1  0  0  0  0  0  0  0  0  0
   -5.7642    1.9599    1.1026 C   0  0  2  0  0  0  0  0  0  0  0  0
   -6.5962    3.1049    0.9819 O   0  0  0  0  0  0  0  0  0  0  0  0
   -5.9609    4.3434    0.0874 P   0  0  0  0  0  5  0  0  0  0  0  0
   -6.2740    4.1167   -1.4264 O   0  0  0  0  0  0  0  0  0  0  0  0
   -4.3462    4.6662    0.2998 O   0  0  0  0  0  1  0  0  0  0  0  0
   -6.8442    5.7621    0.4327 O   0  0  0  0  0  0  0  0  0  0  0  0
   -8.1612    5.3990    0.6410 C   0  0  0  0  0  0  0  0  0  0  0  0
   -7.7851    1.1169    1.9968 O   0  0  0  0  0  0  0  0  0  0  0  0
   -8.1941   -0.0063   -0.7344 N   0  0  0  0  0  0  0  0  0  0  0  0
   -8.9709   -0.6163    0.1938 C   0  0  0  0  0  0  0  0  0  0  0  0
  -10.2420   -1.0409   -0.1735 C   0  0  0  0  0  0  0  0  0  0  0  0
  -10.6421   -0.8461   -1.4558 C   0  0  0  0  0  0  0  0  0  0  0  0
   -9.8494   -0.2824   -2.3726 N   0  0  0  0  0  0  0  0  0  0  0  0
   -8.6078    0.1473   -1.9854 C   0  0  0  0  0  0  0  0  0  0  0  0
   -7.9156    0.6668   -2.8886 O   0  0  0  0  0  0  0  0  0  0  0  0
  -12.0595   -1.0416   -1.7728 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3658   -2.5100   -0.9112 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1868   -4.3388   -0.1653 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.3577   -4.6301    1.0701 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.1837   -5.8725    1.6230 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.5279   -6.8459    0.9694 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0699   -6.5478   -0.2603 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8692   -5.3045   -0.7653 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4073   -5.1193   -1.8981 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7599   -8.1408    1.5024 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.4920   -1.2663   -0.5537 O   0  0  0  0  0  0  0  0  0  0  0  0
    8.3789    0.3918   -0.4780 N   0  0  0  0  0  0  0  0  0  0  0  0
    8.9378   -0.0590   -1.6573 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.2439   -0.4680   -1.6734 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.0000   -0.4392   -0.5599 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.4547    0.0186    0.5974 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.1301    0.4349    0.6281 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.6731    0.8361    1.7090 O   0  0  0  0  0  0  0  0  0  0  0  0
   12.3300   -1.0170   -0.5302 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.3928    4.6824   -0.8172 O   0  0  0  0  0  0  0  0  0  0  0  0
    7.7398    4.7499   -0.7951 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.1790    2.2746    2.4454 H   0  0  0  0  0  0  0  0  0  0  0  0
    5.9414    2.7338    2.2559 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.4746    1.2256    0.0722 H   0  0  0  0  0  0  0  0  0  0  0  0
    6.5767    0.5432   -1.5099 H   0  0  0  0  0  0  0  0  0  0  0  0
    7.1719   -1.2752    0.6264 H   0  0  0  0  0  0  0  0  0  0  0  0
    6.3784    0.1869    2.2796 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.2906   -0.3346    0.8744 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.6470    0.8295   -0.4652 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.1975   -0.9266   -2.0854 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2317   -3.2330   -1.8945 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2205   -2.1835    0.7771 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9100   -0.0149   -0.1884 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.2049    0.0580    0.7069 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0627    1.3414    0.1750 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.7282    2.5930   -0.7393 H   0  0  0  0  0  0  0  0  0  0  0  0
   -7.6287    1.9098   -0.3211 H   0  0  0  0  0  0  0  0  0  0  0  0
   -6.2316   -0.1563    1.4159 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.9850    2.0602    1.8253 H   0  0  0  0  0  0  0  0  0  0  0  0
   -8.1978    4.3338    0.9704 H   0  0  0  0  0  0  0  0  0  0  0  0
   -8.5914    6.0038    1.4782 H   0  0  0  0  0  0  0  0  0  0  0  0
   -8.8002    5.4607   -0.2697 H   0  0  0  0  0  0  0  0  0  0  0  0
   -7.5038    0.7485    2.8961 H   0  0  0  0  0  0  0  0  0  0  0  0
   -8.5798   -0.7555    1.1787 H   0  0  0  0  0  0  0  0  0  0  0  0
  -10.8521   -1.5298    0.5642 H   0  0  0  0  0  0  0  0  0  0  0  0
  -12.4326   -1.6425   -2.4652 H   0  0  0  0  0  0  0  0  0  0  0  0
  -12.7127   -0.4140   -1.1860 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.2554   -2.5080   -1.8881 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.9141   -3.8896    1.6079 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.5883   -6.0801    2.5922 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0503   -8.8840    1.2227 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5154   -8.4067    2.1059 H   0  0  0  0  0  0  0  0  0  0  0  0
    6.0085   -1.5997   -1.3218 H   0  0  0  0  0  0  0  0  0  0  0  0
    8.3689   -0.1065   -2.5651 H   0  0  0  0  0  0  0  0  0  0  0  0
   10.7568   -0.8185   -2.5790 H   0  0  0  0  0  0  0  0  0  0  0  0
   13.1956   -0.5892   -0.8125 H   0  0  0  0  0  0  0  0  0  0  0  0
   12.3860   -2.0450   -0.1676 H   0  0  0  0  0  0  0  0  0  0  0  0
    8.2947    3.9031   -0.3751 H   0  0  0  0  0  0  0  0  0  0  0  0
    8.0930    5.6917   -0.2850 H   0  0  0  0  0  0  0  0  0  0  0  0
    8.0754    4.8072   -1.8767 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  1  3  1  0
  1  4  1  0
  4  5  1  0
  5  6  1  0
  6  7  1  0
  7  8  1  0
  8  9  1  0
  9 10  1  0
 10 11  1  0
 11 12  1  0
 12 13  2  0
 12 14  1  0
 12 15  1  0
 15 16  1  0
 16 17  1  0
 17 18  1  0
 18 19  1  0
 19 20  1  0
 20 21  1  0
 21 22  1  0
 22 23  1  0
 23 24  2  0
 23 25  1  0
 23 26  1  0
 26 27  1  0
 27 28  1  0
 28 29  1  0
 29 30  1  0
 30 31  1  0
 31 32  1  0
 32 33  1  0
 33 34  1  0
 34 35  2  0
 34 36  1  0
 34 37  1  0
 37 38  1  0
 31 39  1  0
 30 40  1  0
 40 41  1  0
 41 42  2  0
 42 43  1  0
 43 44  2  0
 44 45  1  0
 45 46  2  0
 43 47  1  0
 20 48  1  0
 19 49  1  0
 49 50  1  0
 50 51  2  0
 51 52  1  0
 52 53  2  0
 53 54  1  0
 54 55  2  0
 52 56  1  0
  9 57  1  0
  8 58  1  0
 58 59  1  0
 59 60  2  0
 60 61  1  0
 61 62  2  0
 62 63  1  0
 63 64  2  0
 61 65  1  0
  1 66  1  0
 66 67  1  0
 10  6  1  0
 21 17  1  0
 32 28  1  0
 45 40  1  0
 54 49  1  0
 63 58  1  0
  5 68  1  0
  5 69  1  0
  6 70  1  6
  8 71  1  6
  9 72  1  1
 10 73  1  1
 16 74  1  0
 16 75  1  0
 17 76  1  6
 19 77  1  6
 20 78  1  1
 21 79  1  1
 27 80  1  0
 27 81  1  0
 28 82  1  6
 30 83  1  1
 31 84  1  1
 32 85  1  1
 38 86  1  0
 38 87  1  0
 38 88  1  0
 39 89  1  0
 41 90  1  0
 42 91  1  0
 47 92  1  0
 47 93  1  0
 48 94  1  0
 50 95  1  0
 51 96  1  0
 56 97  1  0
 56 98  1  0
 57 99  1  0
 59100  1  0
 60101  1  0
 65102  1  0
 65103  1  0
 67104  1  0
 67105  1  0
 67106  1  0
M  CHG  4   3  -1  14  -1  25  -1  36  -1
M  END
""", removeHs=False)
Chem.AssignStereochemistryFrom3D(before_min)
chirality_before_min = Chem.FindMolChiralCenters(before_min, useLegacyImplementation=False)
chirality_before_min
[(0, 'S'),
 (5, 'R'),
 (7, 'R'),
 (8, 'R'),
 (9, 'S'),
 (11, 'R'),
 (16, 'R'),
 (18, 'R'),
 (19, 'R'),
 (20, 'S'),
 (22, 'S'),
 (27, 'R'),
 (29, 'R'),
 (30, 'R'),
 (31, 'S'),
 (33, 'R')]
after_min = Chem.Mol(before_min)
mp = AllChem.MMFFGetMoleculeProperties(after_min, mmffVariant="MMFF94S")
ff = AllChem.MMFFGetMoleculeForceField(after_min, mp)
ff.CalcEnergy()
264.30454561359454
ff.Minimize(maxIts=10000, forceTol=0.01)
0
Chem.AssignStereochemistryFrom3D(after_min)
chirality_after_min = Chem.FindMolChiralCenters(after_min, useLegacyImplementation=False)
chirality_after_min == chirality_before_min
True
ff.CalcEnergy()
-354.30827119274824

1 reply

petrucci86 May 16, 2022
Author

Thanks very much for your instruction. Highly appreciated!
However, I found that rdMolTransforms.CanonicalizeMol changes the chirality in fact, instead of minimization.
The chirality changes after running:

rdMolTransforms.CanonicalizeMol(compound_mol_h, normalizeCovar=True, ignoreHs=True)

Any thoughts?

ptosco · 2022-05-17T07:53:19Z

ptosco
May 17, 2022
Collaborator

@petrucci86 I cannot reproduce that, and I doubt that's the case, since the canonicalization only implies a rigid body transformation of the molecule's coordinates. See below:

canon_min = Chem.Mol(after_min)
AllChem.CanonicalizeMol(canon_min, normalizeCovar=True, ignoreHs=True)

The molecule has undergone a rigid body transformation, as you can see looking at the RMSD before and after the canonicalization:

AllChem.CalcRMS(canon_min, after_min)
3.172414642034091

Chirality has not changed:

chirality_canon_min = Chem.FindMolChiralCenters(canon_min, useLegacyImplementation=False)
chirality_after_min == chirality_canon_min
True

And the molecules can indeed be realigned reaching a near-zero RMSD, since it was only a rigid-body transformation:

AllChem.GetAlignmentTransform(canon_min, after_min)[0]
9.262903808186189e-08

1 reply

petrucci86 May 17, 2022
Author

Thanks again! I followed your concept and tested it on the molecule I have. I found that its chirality indeed changed.
Please let me know if I misunderstood something. Much appreciated.

A test code is pasted here:

import sys, numpy, rdkit, pyscf, time, py3Dmol
from numpy import loadtxt
from rdkit import Chem, Geometry
from rdkit.Chem import AllChem, ChemicalForceFields, rdMolTransforms, Draw

compound = Chem.MolFromMolBlock("""CREYON GGG TRIMER
     RDKit          3D

115123  0  0  0  0  0  0  0  0999 V2000
    8.2042   -2.4634    3.1848 P   0  0  2  0  0  5  0  0  0  0  0  0
    7.8494   -3.4834    2.1238 O   0  0  0  0  0  0  0  0  0  0  0  0
    7.8138   -2.6951    4.6291 O   0  0  0  0  0  1  0  0  0  0  0  0
    7.6396   -1.0063    2.7027 O   0  0  0  0  0  0  0  0  0  0  0  0
    7.7680    0.1152    3.5679 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.3128    1.3872    2.8602 C   0  0  1  0  0  0  0  0  0  0  0  0
    8.0988    1.5558    1.6567 O   0  0  0  0  0  0  0  0  0  0  0  0
    7.2498    2.2325    0.6908 C   0  0  2  0  0  0  0  0  0  0  0  0
    5.8832    2.4410    1.3458 C   0  0  1  0  0  0  0  0  0  0  0  0
    5.8526    1.3516    2.3989 C   0  0  2  0  0  0  0  0  0  0  0  0
    4.9584    1.6282    3.4643 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.4522    0.9784    3.4851 P   0  0  2  0  0  5  0  0  0  0  0  0
    2.8200    1.3647    4.8079 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.5593   -0.4888    3.1199 O   0  0  0  0  0  1  0  0  0  0  0  0
    2.6139    1.7212    2.2858 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.2464    3.0927    2.4139 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.5986    3.6604    1.1426 C   0  0  1  0  0  0  0  0  0  0  0  0
    2.4788    3.5567    0.0163 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.6723    3.3375   -1.1641 C   0  0  2  0  0  0  0  0  0  0  0  0
    0.2133    3.3102   -0.7152 C   0  0  1  0  0  0  0  0  0  0  0  0
    0.3154    2.9161    0.7475 C   0  0  2  0  0  0  0  0  0  0  0  0
   -0.8028    3.3390    1.5120 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0321    2.3004    1.8353 P   0  0  2  0  0  5  0  0  0  0  0  0
   -2.9865    3.0192    2.7687 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4375    0.9747    2.2670 O   0  0  0  0  0  1  0  0  0  0  0  0
   -2.8089    2.0481    0.4126 O   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5773    3.0909   -0.1820 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.1051    2.7174   -1.5726 C   0  0  1  0  0  0  0  0  0  0  0  0
   -3.0592    2.4160   -2.4956 O   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5069    1.4069   -3.4170 C   0  0  2  0  0  0  0  0  0  0  0  0
   -4.9474    1.0847   -3.0352 C   0  0  1  0  0  0  0  0  0  0  0  0
   -5.0103    1.4902   -1.5683 C   0  0  2  0  0  0  0  0  0  0  0  0
   -6.3259    1.8118   -1.1533 O   0  0  0  0  0  0  0  0  0  0  0  0
   -7.2397    0.6938   -0.3787 P   0  0  2  0  0  5  0  0  0  0  0  0
   -8.5428    1.3520    0.0250 O   0  0  0  0  0  0  0  0  0  0  0  0
   -6.3938   -0.0082    0.6627 O   0  0  0  0  0  1  0  0  0  0  0  0
   -7.5357   -0.3592   -1.5932 O   0  0  0  0  0  0  0  0  0  0  0  0
   -8.3938    0.0106   -2.6592 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.7829    1.9282   -3.8299 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.6110    0.2634   -3.3539 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.4041   -0.6383   -4.3635 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4262   -1.4789   -3.8867 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9536   -2.5536   -4.7147 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0876   -3.3483   -4.3712 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.6126   -2.5582   -5.9505 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.6119   -1.6397   -6.3441 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0283   -0.6667   -5.5644 N   0  0  0  0  0  0  0  0  0  0  0  0
   -3.1227   -1.8316   -7.6012 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0178   -1.1344   -2.6346 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7444   -0.0735   -2.3431 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2656    4.6518   -0.8403 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.0870    2.1015   -1.8143 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.7504    1.7238   -3.0873 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3008    0.4731   -3.2379 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1171   -0.2350   -4.4741 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5844   -1.3440   -4.7000 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.3346    0.5106   -5.3647 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.8024    1.7932   -5.1035 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.0046    2.4283   -3.9705 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.0555    2.3352   -6.1164 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.9508    0.0592   -2.1156 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.7868    1.0548   -1.2666 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.9167    3.7336    1.9549 O   0  0  0  0  0  0  0  0  0  0  0  0
    7.1601    1.4424   -0.5316 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.6121    1.8757   -1.7117 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.5983    0.7643   -2.5206 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.0300    0.8560   -3.8373 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.9802   -0.0802   -4.6250 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.5379    2.1446   -4.0800 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.5942    3.2226   -3.1684 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.1372    3.1160   -1.9760 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.0404    4.3950   -3.6119 N   0  0  0  0  0  0  0  0  0  0  0  0
    7.1144   -0.3306   -1.8970 N   0  0  0  0  0  0  0  0  0  0  0  0
    7.4228    0.1042   -0.6906 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.8135   -2.1697    3.1305 O   0  0  0  0  0  0  0  0  0  0  0  0
   10.4457   -2.0051    1.8723 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.8215    0.2100    3.8504 H   0  0  0  0  0  0  0  0  0  0  0  0
    7.1718   -0.0558    4.4697 H   0  0  0  0  0  0  0  0  0  0  0  0
    7.5002    2.2436    3.5205 H   0  0  0  0  0  0  0  0  0  0  0  0
    7.7453    3.1731    0.4234 H   0  0  0  0  0  0  0  0  0  0  0  0
    5.0241    2.4145    0.6724 H   0  0  0  0  0  0  0  0  0  0  0  0
    5.6160    0.3916    1.9270 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.5514    3.1876    3.2548 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.1441    3.6673    2.6474 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.3890    4.7240    1.3148 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.8905    4.1519   -1.8648 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4500    2.6635   -1.2935 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.4591    1.8326    0.8245 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.9513    3.9803   -0.2596 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.4175    3.3215    0.4813 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.6509    3.5876   -1.9609 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.4212    1.8275   -4.4257 H   0  0  0  0  0  0  0  0  0  0  0  0
   -5.2480    0.0488   -3.2148 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.5795    0.6944   -0.9505 H   0  0  0  0  0  0  0  0  0  0  0  0
   -8.5550    1.0911   -2.6900 H   0  0  0  0  0  0  0  0  0  0  0  0
   -9.3558   -0.4905   -2.5268 H   0  0  0  0  0  0  0  0  0  0  0  0
   -7.9479   -0.3161   -3.6016 H   0  0  0  0  0  0  0  0  0  0  0  0
   -6.6754    1.8983   -3.4495 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3510   -3.2801   -6.6154 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7963   -2.5853   -8.1959 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.8446   -1.2235   -7.9721 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.6810    0.4802   -1.4179 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1002    4.7142   -0.3501 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.1331    0.0944   -6.2690 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3715    3.2501   -6.0209 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0997    1.8359   -6.9852 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.1579    1.0652   -0.2523 H   0  0  0  0  0  0  0  0  0  0  0  0
    5.1659    3.7905    2.5669 H   0  0  0  0  0  0  0  0  0  0  0  0
    5.1024    2.3152   -4.9817 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.6182    4.4665   -4.5310 H   0  0  0  0  0  0  0  0  0  0  0  0
    5.0285    5.2232   -3.0268 H   0  0  0  0  0  0  0  0  0  0  0  0
    7.8362   -0.5082    0.0972 H   0  0  0  0  0  0  0  0  0  0  0  0
    9.9754   -1.1901    1.3171 H   0  0  0  0  0  0  0  0  0  0  0  0
   10.3844   -2.9333    1.2989 H   0  0  0  0  0  0  0  0  0  0  0  0
   11.4973   -1.7597    2.0394 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  1  3  1  1
  1  4  1  0
  4  5  1  0
  5  6  1  0
  6  7  1  0
  7  8  1  0
  8  9  1  0
  9 10  1  0
 10 11  1  0
 11 12  1  0
 12 13  2  0
 12 14  1  6
 12 15  1  0
 15 16  1  0
 16 17  1  0
 17 18  1  0
 18 19  1  0
 19 20  1  0
 20 21  1  0
 21 22  1  0
 22 23  1  0
 23 24  2  0
 23 25  1  1
 23 26  1  0
 26 27  1  0
 27 28  1  0
 28 29  1  0
 29 30  1  0
 30 31  1  0
 31 32  1  0
 32 33  1  0
 33 34  1  0
 34 35  2  0
 34 36  1  1
 34 37  1  0
 37 38  1  0
 31 39  1  0
 30 40  1  0
 40 41  1  0
 41 42  2  0
 42 43  1  0
 43 44  2  0
 43 45  1  0
 45 46  1  0
 46 47  2  0
 46 48  1  0
 42 49  1  0
 49 50  2  0
 20 51  1  0
 19 52  1  0
 52 53  1  0
 53 54  2  0
 54 55  1  0
 55 56  2  0
 55 57  1  0
 57 58  1  0
 58 59  2  0
 58 60  1  0
 54 61  1  0
 61 62  2  0
  9 63  1  0
  8 64  1  0
 64 65  1  0
 65 66  2  0
 66 67  1  0
 67 68  2  0
 67 69  1  0
 69 70  1  0
 70 71  2  0
 70 72  1  0
 66 73  1  0
 73 74  2  0
  1 75  1  0
 75 76  1  0
 10  6  1  0
 21 17  1  0
 32 28  1  0
 50 40  1  0
 47 41  1  0
 62 52  1  0
 59 53  1  0
 74 64  1  0
 71 65  1  0
  5 77  1  0
  5 78  1  0
  6 79  1  1
  8 80  1  6
  9 81  1  6
 10 82  1  6
 16 83  1  0
 16 84  1  0
 17 85  1  1
 19 86  1  6
 20 87  1  6
 21 88  1  6
 27 89  1  0
 27 90  1  0
 28 91  1  6
 30 92  1  6
 31 93  1  1
 32 94  1  1
 38 95  1  0
 38 96  1  0
 38 97  1  0
 39 98  1  0
 45 99  1  0
 48100  1  0
 48101  1  0
 50102  1  0
 51103  1  0
 57104  1  0
 60105  1  0
 60106  1  0
 62107  1  0
 63108  1  0
 69109  1  0
 72110  1  0
 72111  1  0
 74112  1  0
 76113  1  0
 76114  1  0
 76115  1  0
M  CHG  4   3  -1  14  -1  25  -1  36  -1
M  END
""", removeHs=False)


compound_canon = Chem.Mol(compound)
AllChem.CanonicalizeMol(compound_canon, normalizeCovar=True, ignoreHs=True)
print(AllChem.CalcRMS(compound_canon, compound))

chirality_compound = Chem.FindMolChiralCenters(compound, useLegacyImplementation=False)
chirality_compound_canon = Chem.FindMolChiralCenters(compound_canon, useLegacyImplementation=False)

print(chirality_compound == chirality_compound_canon)

print(AllChem.GetAlignmentTransform(compound_canon, compound)[0])

Chem.MolToXYZFile(compound, "compound.xyz")
Chem.MolToXYZFile(compound_canon, "compound_canon.xyz")

ptosco · 2022-05-18T07:05:39Z

ptosco
May 18, 2022
Collaborator

@petrucci86 Ouch, that's a bug indeed. Apparently CanonicalizeMol() has generated the mirror image of the starting coordinates:

print(chirality_compound)
print(chirality_compound_canon)
[(0, 'R'), (5, 'R'), (7, 'R'), (8, 'R'), (9, 'S'), (11, 'R'), (16, 'R'), (18, 'R'), (19, 'R'), (20, 'S'), (22, 'R'), (27, 'R'), (29, 'R'), (30, 'R'), (31, 'S'), (33, 'R')]
[(0, 'S'), (5, 'S'), (7, 'S'), (8, 'S'), (9, 'R'), (11, 'S'), (16, 'S'), (18, 'S'), (19, 'S'), (20, 'R'), (22, 'S'), (27, 'S'), (29, 'S'), (30, 'S'), (31, 'R'), (33, 'S')]

for i in range(compound_canon.GetConformer().GetNumAtoms()):
    coord = compound_canon.GetConformer().GetAtomPosition(i)
    coord.x = -coord.x
    compound_canon.GetConformer().SetAtomPosition(i, coord)
Chem.AssignStereochemistryFrom3D(compound_canon)
chirality_compound_canon = Chem.FindMolChiralCenters(compound_canon, useLegacyImplementation=False)
print(chirality_compound == chirality_compound_canon)
True

That should not happen. I am filing this as a bug (#5303).
Many thanks for reporting!

1 reply

petrucci86 May 19, 2022
Author

No problem. Just wondering that is there any other ways to place the molecule in the origin and align along z axis? Thanks again.

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Chirality change after constraint geometry minimization using MMFF #5292

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